Truvada: Troubles Ahead?

Dave R writes...the use of Truvada as an HIV prevention tool, PrEP, has caused waves of excitement in many quarters but is it a case of premature exhilaration, leading to unwanted consequences!

Sometimes a sort of HIV-related sixth sense kicks in and you get that feeling in your water that the latest advance regarding prevention and treatment just doesn’t ring true. Do you feel that occasionally? This story about Truvada, being used as a prevention tool, (PrEP) just gives me the chills. It’s as if they just haven’t taken into account the foibles of human nature when it comes to doing what you’re supposed to do.

Let me start by disclaiming. I’m not a doctor but I have been on Truvada twice in my HIV treatment history. Eventually, thanks to kidney problems and possible other side effect issues, it was dropped from my triple therapy. This left me on a ‘double therapy’ with double doses Isentress, Prezista and Norvir. Thankfully, after two years, it’s the best-working regime so far.

So maybe personal experience has made me biased against Truvada. However, being biased because you don’t like something is one thing; because it’s doing you harm is entirely different. Kidney problems are a quite common side effect of long term use of the drug; along with stomach problems, loss of bone density, hepatoxicity in the liver, with liver enlargement and fatty deposits close behind and some people have experience the dread of most HIV patients, lipodystrophy. Granted these are the more serious possible side effects; much more common are: diarrhoea, dizziness, nausea, headache, fatigue, abnormal dreams, sleeping problems, rash, and depression. I’m not exaggerating; these come directly from Gilead’s very own, Truvada.com and it’s common sense to assume that it’s in a drug company’s nature to play it down whilst still telling the truth, especially if they’re on the verge of a multi-million dollar boost in sales. Still want to take this every day boys? Remember, you’re not ill in the first place and they’re going to prescribe you something that most definitely isn’t M & M’s.

Why was Truvada the chosen one?

It goes without saying that without a cure for HIV on the horizon, a pill like this is exactly what both authorities and people susceptible to HIV (in other words, theoretically every person having sex), have long been looking for. However, all new treatments have to get by the guardians of our health, the FDA (US Food and Drug Administration), which like Moses on the mount; the rest of the world most often follows. The fact that they have approved recommendations put to them by their own advisory panel is a huge step.

However, in this case, the FDA advisory panel seems to me, to have somewhat succumbed to wishful thinking (am I allowed to say that about such an august body?) The findings and data for the approval of Truvada as PrEP (Pre-Exposure Prophylaxis) emerged largely from two placebo-controlled trials consisting of less than 5,000 participants each. The first was the Pre-Exposure Prophylaxis Initiative (iPrEx), sponsored by the U.S. National Institutes of Health and the Bill and Melinda Gates Foundation and the second; Partners PrEP, sponsored by the University of Washington and funded by the Bill and Melinda Gates Foundation. Other much smaller trials in Africa and South America, amongst others, were taken into consideration. Both the large trials seemed to support a reduced risk of infection of between 42% and 75%. Not exactly 100% reassurance, you might think, and they didn’t look at behavioural trends amongst potential target groups but hey, these are big guns in the research world, so they must be right...right!

"This approval is a major milestone in our 30-year fight against AIDS," said Robert M. Grant, who was the chief investigator of the iPrEx trial..."The use of PrEP alongside routine HIV testing gives us a tremendous opportunity to reduce the rate of new HIV infections in this country and around the world."

All well and good; the results seems to give protection to between 4 out of 10 and 7 out of 10 respectively. Is an average of five and a bit people out of every ten good enough? Not on its own, no. It requires a strict regime of alternative protection, testing and adherence (I had to laugh at that one!)

So what are the obligations on the person taking it?

First of all; you must not have HIV already! You can double underline that one; the risks of creating drug resistance are surely obvious. So how long will it be before the first ten thousand, twenty-something’s start taking it whilst already being knowingly or unknowingly infected? One assumes everybody will be tested rigorously beforehand...that will happen in every land won’t it?

You also mustn’t have hepatitis B. Truvada is definitely a no-no in that respect.

You will need to be regularly tested during the first few months of taking it, both for HIV infection and all the other potential issues of bone density, renal impairment and so on.

You must undergo initial and then regular counselling (yeah that’s going to work!)

You need to be in a high risk group. Sero-discordant couples, both gay and straight, come to the front of the queue but in general it means all those who regularly have sex with, or are themselves high risk individuals, including sex-workers, etc. Will people have to prove they belong to a ‘high risk’ group? I wouldn’t put it past certain North American authorities to demand proof of some sort and then the privacy factor comes into play. What happens to that information then? The real high risk groups, including married men, cultural, ethnic and religious groups, who by nature have sex secretly, will never come out openly in order to use Truvada.

Here’s the one that made me giggle nervously. Experts strongly advise the use of condoms as well. Uhm, pause for that to sink in...condoms! Tell me, if you’re supposed to use condoms, what the hell’s the point of taking high strength chemicals for the rest of your life on top? Condoms are PrEP, or am I wrong?

And you’re supposed to do all this as back-up, with only an average 50% chance of your preventing infection anyway! I’m beginning to get the feeling that the emperor has no clothes here.

So why won’t it work?

I have to point out here that this is only my opinion; it’s not an expert opinion and it’s open to being shot down. However, the Dutch have a saying that someone can be an ‘ervaringsdeskundige’ which basically means that you become an expert based on experience. Isn’t every long-term HIV patient a sort of ‘experience expert’ and doesn’t that also have value, despite not having medical degrees or years of research lab experience?

In my view, we have to look at what the target group for Truvada as a prevention tool may be. These are people who don’t already have HIV and are therefore by and large somewhat younger. Between 18 and 30 seems to be a reasonable guess. They are deemed to be ‘high risk’ individuals, who are having sex with partners who may or may not have HIV. Let’s take out the sero-discordant couples (for clarity; those where one partner is already HIV positive and the other isn’t) because this sort of pill seems to be of definite value to them. Then again, if you’re in such a relationship, you’re unlikely to be a twenty-something newbie on the block, don’t you think? So that leaves us with a huge group of young people for whom Truvada may be both relevant and desirable.

This is where my gut feeling screams, ‘Are you f...ing kidding me!’ Are they seriously expecting the majority of virile youngsters, hitting the scene for the first time and letting their hormones run amok, to obey the rules? They may, in the beginning and some may forever, but really, did these research trials even look at how young people behave? What are those youngsters expected to do? Let’s just take the three main things: take a pill every day; get tested every month; and wear a condom during sex. I know, right; if it wasn’t so serious you might laugh out loud. Let’s assume that 50% of all people who eventually start taking Truvada as PrEP, are intelligent and responsible and will do the right thing...all the time (and that’s a big ask!) What about the rest; who we know will get drunk or stoned out of their heads; forget the pill for one or more days; will almost certainly not stick to a testing regime and will start using Truvada as a party drug to be taken when the mood takes them? That’s not taking into account the fact that many will assume that they don’t need to use a condom ever again! There’s little doubt about this; young guys just don’t think straight; they’re ruled by their hormones and their genitals and logic sometimes just doesn’t stand a chance. The only hope is that the fear of other STD’s will be enough to prolong condom use. The spectre of Hepatitis C, for instance, must be enough to put the fear of God into most teenagers! Will the medical authorities ever have a handle on the whole business and be able to monitor all patients (if you take Truvada, you’re a patient in my book) and enforce the rules? Hello...financial cuts...the cost of Truvada alone on this scale, is going to test even the best kept budgets! In a practical sense, efficient control seems unworkable.

So what happens then?

Ten years down the line, my fear is that resistance to Truvada has crossed the world and is impossible to reverse. Do the powers that be realise that Truvada is the most widely used basis for world-wide HIV combinations? Of course they do, I’m not suggesting that they haven’t looked at all the possibilities but so far I haven’t seen a cogent reason as to why Truvada is a secure option to avoid resistance.

We all know that the pressure from all sides to come up with a solution to the HIV problem is enormous. Every lobby and interest group going is exerting pressure to come up with something. I just wonder if Truvada is a common sense option or a recipe for HIV disaster and will eventually achieve the complete opposite of what it’s intended to do. It’s not 100% reliable; it carries significant possible side effects; it’s tied to a whole battery of rules based on self-control and it runs the risk of major abuse and consequences for the whole HIV community. Are you sure FDA...really sure?